A study of the inflammatory reaction following the injection of dextrans (60 mg) of various molecular weights cpd. 48/80 or antiserum to IgE (anti-IgE) into the rat pleural cavity revealed several distinct responses. The dextrans into the rat pleural cavity revealed several distinct responses. The dextrans induced accumulation of fluid with little protein and few neutrophils. The exudate induced by cpd. 48/80 contained fluid and plasma proteins. Both responses were of rapid onset (30 min) and were accompanied by mast cell degranulation. Antiserum to IgE also induced mast cell degranulation and rapid accumulation of fluid and protein, and at a later stages (4h) an infiltration of neurotrophils. All these responses were unaffected by indomethacin. The response to anti-IgE was partially blocked by treatment with either metiamide or mepyramine (a H2 and H1 receptor antagonist respectively) and completely blocked when both drugs were given simultaneously. Fluid volume and protein content were reduced to a simiextent (99% and 91%, respectively), whereas leukocyte infiltration was reduced by only 46%. These and our previous studies suggest that inflammatory infiltrates may be formed through two distinct mechanisms: one associated with transudation of protein-free fluids, the other to exudation of plasma proteins.